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Combined blockade of integrin-α4β1 plus cytokines SDF-1α or IL-1β potently inhibits tumor inflammation and growth

Title
Combined blockade of integrin-α4β1 plus cytokines SDF-1α or IL-1β potently inhibits tumor inflammation and growth
Authors
Schmid M.C.Avraamides C.J.Foubert P.Shaked Y.Kang S.W.Kerbel R.S.Varner J.A.
Ewha Authors
강상원
SCOPUS Author ID
강상원scopus
Issue Date
2011
Journal Title
Cancer Research
ISSN
0008-5472JCR Link
Citation
vol. 71, no. 22, pp. 6965 - 6975
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Tumor-associated macrophages promote tumor growth by stimulating angiogenesis and suppressing antitumor immunity. Thus, therapeutics that inhibit macrophage recruitment to tumors may provide new avenues for cancer therapy. In this study, we showed how chemoattractants stromal cell-derived growth factor 1 alpha (SDF-1α) and interleukin 1 beta (IL-1β) collaborate with myeloid cell integrin-α4β1 to promote tumor inflammation and growth. We found that SDF-1α and IL-1β are highly expressed in the microenvironments of murine lung, pancreatic, and breast tumors; surprisingly, SDF-1α was expressed only by tumor cells, whereas IL-1β was produced only by tumor-derived granulocytes and macrophages. In vivo, both factors directly recruited proangiogenic macrophages to tissues, whereas antagonists of both factors suppressed tumor inflammation, angiogenesis, and growth. Signals induced by IL-1β and SDF-1α promoted the interaction of talin and paxillin with the cytoplasmic tails of integrin-a4b1, thereby stimulating myeloid cell adhesion to endothelium in vitro and in vivo. Inhibition of integrin-α4β1, SDF-1α, or IL-1β was sufficient to block tumor inflammation and growth, and the combined blockade of these molecules greatly accentuated these effects. Furthermore, antagonists of integrin-α4β1 inhibited chemotherapy-induced tumor inflammation and acted synergistically with chemotherapeutic agents to suppress tumor inflammation and growth. These results show that targeting myeloid cell recruitment mechanisms can be an effective approach to suppress tumor progression. ©2011 AACR.
DOI
10.1158/0008-5472.CAN-11-0588
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자연과학대학 > 생명과학전공 > Journal papers
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